REVIEW article
Front. Cell Dev. Biol.
Sec. Signaling
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1547582
This article is part of the Research TopicRedox Signaling in Metabolism, Development, and AgingView all articles
KRAS and NRF2 Drive Metabolic Reprogramming in Pancreatic Cancer Cells: Role of Oxidative and Nitrosative Stress
Provisionally accepted
- 1Department of Medicine, Udine, Italy
- 2University of Udine, Udine, Italy
- 3Agricultural Food Environmental and Animal Science, Udine, Italy
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Cancer cells are subject to metabolic reprogramming, which leads to a sustained production of reactive oxygen species (ROS). Increased oxidative stress contributes to genomic instability and promotes malignant transformation. To counteract excessive ROS levels, cells activate nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of redox homeostasis that coordinates the transcription of a wide range of antioxidant and cytoprotective genes. This review examines the metabolic adaptations controlled by the KRAS-NRF2 axis under oxidative stress conditions. In addition, we highlight a novel function of NRF2 in regulating the expression of NOS2 by binding to a DNA enhancer element, thereby modulating the production of reactive nitrogen species (RNS). Finally, we discuss novel molecular strategies aimed at disrupting adaptive antioxidant responses in cancer cells and provide insights into combinatorial therapeutic approaches targeting redox balance in cancer.
Keywords: KRAS, Nrf2, Nos2, metabolic reprogramming, PDAC, ROS, RNS
Received: 18 Dec 2024; Accepted: 26 May 2025.
Copyright: © 2025 Rapozzi, Comuzzi, Di Giorgio and Xodo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Luigi Emilio Xodo, University of Udine, Udine, Italy
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